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Addison’s
Disease in Your Dog
Treating Hypoadrenocorticism

Ron Hines DVM PhD

You can read more extensive veterinary reviews of Addison's disease here & here

Some
dogs develop just the opposite problem, their adrenal glands produce
too much cortisol. You can read about that problem here.

What
Is Addison’s Disease(or Hypoadrenocorticism) ?

I am going to tell you some things about hypoadrenocorticism –
a long word for a comparatively simple, but very serious,
disease that Dr.
Addison recognized well over a hundred years ago.
We still call it Addison’s because it is a much easier word to say than its scientific name. (You can read
the good Dr.’s diaries here) Both you and your pet have a lima bean-shaped gland
just above/ahead of each kidney - the adrenal
glands . Although they are quite small, they have two very critical
functions. Their outer layer, the cortex,
produces cortisol (a glucocorticoid) hormone which we all must have to deal with stress. It also produces a second hormone, aldosterone (a mineralcorticoid), which one must have to regulate the amount of salt in our bodies. Cortisol also decreases inflammation, increases blood sugar, suppress
the immune system, increase the production of fat and decrease the
number of certain white blood cells called lymphocytes that are involved in immunity.

The adrenals
produce more cortisol in stressful situations (both
physical and mental stress) than when your dog is calm. The aldosterone, or salt-regulating hormone that the outer adrenal
gland layer also produces regulates the amount of sodium (Na) and potassium (K)
in your pet’s blood. Both Na and K need to be kept
within tight limits in order for your pet’s body to function
correctly. The inner layer of the adrenal gland is called its medulla. It
plays little part in Addison’s disease. The medulla (medullary
portion) produces the epinephrine we also use to deal with sudden stressors.

Is Addison's Disease A Common Problem In Dogs ?

Addison’s
disease is not a common disease in dogs. Its mirror image, Cushing’s disease, is much more
common in dogs. But veterinarians think and talk about Addison’s alot. That is because pets with Addison's come through our clinic doors "pretending"
to have so many other health issues. It often it takes
repeated office visits, frustrated clients and perplexed veterinarians, before the light bulb comes on in our head and the word, Addison’s, flashes through our minds. Once that happens, the diagnosis and treatment
of your pet are usually quite straightforward. Addison’s
disease occurs in both sexes. It appears to be a bit more common
in female dogs. Dogs that develop the problem are usually over 5.5
years of age when major signs are first noticed. But because the destructive
processes that lead to Addison’s disease occur slowly, these pets were in the process of loosing their adrenal gland
function considerably earlier than that. Occasionally, an elderly dog
will develop Addison’s disease as part of a malignancy situation.
(ref)

Are
Certain Dogs More Susceptible Than Others ?

Yes.

Some
breeds do develop Addison's disease more frequently than others. Genetic predisposition occurs
when a breed or a line of dogs relies on too few ancestor founding animals. That
is, all dogs in the breed or line are too closely related (inbred). These
high-incidence breeds include Portuguese
water dogs (ref), duck-trolling
retrievers, standard
poodles (ref), wheaten terriers, great danes, and the westies. But any
dog has the potential to develop Addison’s disease.

Is
There More Than One Form Of Addison's Disease ?

Yes.

Veterinarians recognize three forms of Addison’s disease:

Typical (Primary adrenal form):

In
the majority of pets that develop Addison’s disease, their problem
is destruction or loss of the cells that produce cortisol and aldosterone
in their adrenal gland cortex (AZF cells in the zona fasciculata). (ref) In these pets, their immune system has mistakenly
identified these cells as foreign to the pet’s body - seen as something
that shouldn’t be there that needs to be destroyed. This
is what occurs in all autoimmune diseases. You can read
all about autoimmune diseases in general here In dogs, over-vaccination can be one of the causes. (ref)

Secondary (Pituitary
form):

Less frequently, a messenger hormone, ACTH , that is normally produced
in your pet’s pituitary gland ceases to flow adequately.
Without ACTH, the cells in the dog's adrenal cortex that normally produce
cortisol and aldosterone do not do so. This less-common type
of Addison’s disease is called secondary or pituitary-based
or Addison’s disease. I
see Addison’s disease more than I should in dogs that have
received multiple injections of long-acting steroid hormones (Methylprednisolone
acetate=”Depo”) as a “quick fix”
for itchy skin. NEVER allow that form of treatment for your dog's allergic
skin problems (atopy) and think twice
before attempting to relieve moderate itchy allergies with Atopica as well. When due to overzealous corticosteroid administration and then discontinuing those drugs - particularly abruptly - it would be called iatrogenic Addison' disease.

Atypical form:

The
adrenal cortex is, itself divided into three layers (zona
fasciculate, zona reticularis, zona glomerulosa). Usually,
but not always, all three layers become dysfunctional together.
However, the topmost layer, in the zona
glomerulosa, is sometimes spared. It is the one most responsible
for making aldosterone – the hormone that controls the body's salt
concentration (sodium and potassium).
This portion of the zona glomerulosa will occasionally continues to function while
the other two cortisol-secreting layers fail. This is sometimes called Atypical
Addison’s disease. In these atypical cases, the pet only needs
to be given cortisol-like drugs (prednisolone,
prednisone, etc.) to keep it stable. It is also common for dogs with the pituitary form of Addison's
to also continue to make sufficient aldosterone (mineralcorticoid)
. Those dogs too can be maintained on a corticosteroid alone. The
severe "crashes" vets see in Addison’s dogs are usually in the
ones that have the most serious problems in the outermost layer. They are the
ones that develop electrolyte imbalances that send them to emergency
animal hospitals. When
a pet has had an abnormal ACTH stimulation test, there is a very
good chance that eventually, all three layers of the adrenal cortex
will fail – even if the pet’s blood electrolytes come
back normal or close to normal for now. "Atypical" can mean different things to different veterinarians. So the term "atypical" can be use to describle conditions that are not quite alike. But you can read about some individual cases here.

What
Are They Symptoms of Addison’s Disease ?

Addison’s
disease (hypoadrenocorticism) is
a chronic disease. That means it develops gradually, with ever-increasing
signs. So the first symptoms your dog experiences will probably
be written off to something else: Too much exercise or excitement,
indigestion, a mild “bug” the pooch caught at the doggy park,
etc, etc. Those early signs often include listlessness, weakness, vomiting,
diarrhea or loss of appetite that come and go. Because
early Addison’s symptoms are mild and come and go naturally, vets often treat these cases symptomatically with anti-vomit medications
(anti-emetics) anti-diarrheal medications,
bland diets and perhaps some antibiotics like metronidazole (Flagyl).
The dogs get better, so the complicated diagnostic tests don’t
get run. But with time and repeat incidents, veterinarians and owners often put two and two together. They realize that these
health crises are occuring shortly after stress – a big party, guests
in the home, rowdy kids, a period at the boarding kennel, stress in the household etc. Because
Addison’s disease is usually progressive, the time often eventually comes when
the dog becomes quite ill. At that point (often
at some nighttime emergency clinic) blood electrolytes
do get measured and, if the veterinarian is astute, the possibility
of Addison’s disease comes up. Those dogs are in what we call
an “Addsonian crisis”. This is a form of shock and collapse
of the circulatory system than can be fatal. Some
pets do not present with these classical signs. They might be brought
in with very low blood sugar levels (hypoglycemia)
or seizures or muscle tremors or heart beat irregularities. So they
might be misdiagnosed as having reoccurring pancreatitis, kidney
or heart disease. The most telling thing I have seen in these masquerading
cases - the thing that should alert owners
and veterinarians alike - is a pet that enters the emergency
clinic one night looking like he or she is on death’s doorstep and
leaves the next day looking fit as a fiddle with a muddled diagnosis. Occasional
cases of Addison’s disease present as an inability to fully
swallow or a pet that repeatedly regurgitates (vomits)
undigested food (megaesophagus).You can read a little quiz given to veterinarians about Addison's here.

Can
Addison’s Disease Be A Life-threatening Emergency ?

Yes,
a circulatory collapse (Addisonian crisis)
can be fatal if the changes in blood electrolyte levels (sodium too
low, potassium too high)
are not quickly corrected. This requires substantial amounts
of intravenous fluids, supportive care and close monitoring. If
the pets blood sugar levels have dropped abnormally low, they need
to be elevated. If diarrhea and vomiting have dehydrated the animal,
that needs to be quickly corrected as well. Rapidly-acting
corticosteroid medications such as intravenous prednisolone sodium succinate or
dexamethasone sodium phosphate often improve the situation too.

Are
There Other Health Problems That Could Be Confused With Addison’s
Disease ?

Yes.

After reading this far, you already understand that many health issues can
be easily confused with Addison’s disease – particularly in its early stages. Some
Addison’s case are at first confused with acute pancreatitis. (ref)
Others get confused with hypoglycemia, food poisoning, parvovirus enteritis (ref), gastric volvulus (ref), intussuceptions (ref) and spinal or joint problems (ref). Tests that diagnose Addison's disease definitively are time consuming and expensive. So they are often put off.

It
is more common for dogs, showing early non-specific symptoms to be given intravenous
fluids, like lactated ringers solution (LRS), along with corticosteroid injections. Just by coincidence, that
happens to be quite similar to the specific treatments for an Addisonian
crisis. So the pet gets better without the veterinarian or owner really knowing
why. For reasons we do not understand, it appears to some that whipworms can affect a dog’s
sodium and potassium levels much like Addison’s disease does.
You can read about that here.
If you suspect Addison’s disease but ACTH tests are normal,
giving your pet a monthly heartworm control product or wormer that
also controls whipworms might be prudent.

What
Tests Will My Vet Run To Diagnose The Problem ?

Abnormally
high blood potassium level and abnormally low blood sodium levels
can alert veterinarians to the possibility of Addison’s disease,
but they are not enough to diagnose it. The levels of both can be
normal in your pet’s blood samples when it is between major
crises. Low urine specific gravity (urinalysisspecific gravity too dilute [ref])
high levels of metabolic waste in the blood (elevated
BUN and Creatinine) and increased body acidity (metabolic
acidosis) are also common in Addison's disease; but
they also occur in many health problems not related to your pet’s
adrenal glands. You can see what the normals are for all these values
in your dog here.

The
best way veterinarians have to diagnose Addison’s
disease in 2018 is through an ACTH stimulation test. In this test, a blood
sample is taken from your pet and the level of cortisol in it is
measured. After that, a small amount of cosyntropin (Cortrosyn™ or Synacthen® ), products similar to your dog's pituitary hormone ACTH, is injected
into your pet. After a period of time, another blood sample is taken
from the pet. When the adrenal glands are working normally, that
injection will cause your pet’s blood cortisol levels to rise
significantly. When it does not, it is evidence that the pet’s
adrenal glands do not have the reserve capacity they need to produce additional cortisol. This is the definitive test for primary Addison's disease. When pre-test cortisol levels are consistently low, and post test levels rise dramatically, secondary Addison's disease needs to be considered. Those rarer pets still have functional adrenal glands, the glands are just not receiving enough ACTH messenger chemical from the pituitary gland to stimulate their adrenal gland cortisol production.

Low
Dose ACTH Stimulation Test

In
the USA, Cortrosyn has been quite expensive. So veterinarians have adapted
the test to work with smaller amounts of the drug. You can read
about that here. In 2014, veterinarians at Mississippi State and Purdue universities reported that a single blood assay of the pet's Cortisol-to-ACTH Ratio was an effective way to diagnose Addison's disease. But as of mid 2016, I know of no laboratories offering the test. (ref1, ref2)

Ideas
That Went Nowhere

There
was some thought that a doppler ultrasound examination of your pet
might detect abnormal adrenal glands. An article on that was published
in 1997. (ref)

21-Hydroxylase Assay

Humans
that develop Addison’s disease usually develop it because they have a form
of autoimmune disease. That was thought to also be the case in dogs.
In humans, a test now exists that measures the amount of antibodies
(or autoimmunity) a person has developed
against his own adrenal glands (21OHAb antibodies). There should not be any. It
would be wonderful if we had such a test for dogs. If we did, we
could detect the disease in its early stages when the ACTH test
results are borderline. Perhaps we could also use such a test to
choose which dogs we ought to breed and which ones we shouldn’t
. However,
the test kits used by human diagnostic labs (Kronus
Labs) do not seem to work in dogs. Using these tests
to detect 21OHAb in their serum has been consistently negative for
their presence. I do not know why. Perhaps the form of Addison's
disease that dogs develop is not as similar to the form humans develop
as we once thought. A
research team at the Veterinary school of Michigan State University,
was attempting to determine if the test
might be modified and applied to dogs. I do not know the current
status of his research.

Lymphocyte Count and Sodium:Potassium Ratio

A recent study found that dogs with Addison's disease tended to have high-end lymphocyte counts along with abnormally low sodium:potassium ratios (less than 27). (ref) The CBC/ WBC and blood chemistry tests that give those values may have already been performed on your dog.

Genetic
Markers

Another
group at the veterinary school in Davis CA attempted to locate
genetic markers that might indicate that a dog was prone to developing
Addison’s disease. I do not know the current status of that project.

Are There Simple Things I Can Do At Home To Monitor My Dog's Treatment ?

Yes.

Besides returning to normal blood sodium and potassium concentrations,
dogs with Addison's disease that is well controlled should return
to producing normal urine volume. Not all dogs with uncontrolled
Addison's disease drink and pee excessively - but many do. They do
so because they lack cortisol and, in many cases, aldosterone hormone as
well. You can read about that here.
So dogs that have their Addison's disease well controlled with medications
should produce more concentrated urine. It is quite simple for you
to measure your dog's urine concentration at home. Many of my clients
, dealing with other health conditions, do. To see how the test
is done, go here. Remember,
many things can cause urine to be excessively dilute: the loss of
kidney function that occurs in many older dogs (ref), diabetes, etc. So
your pet's urine concentration (its specific
gravity) needs to be considered in light of the pet's
total health picture. Overly-concentrated urine brings its own set of problems. There is a fuller explaination about urine specific gravity in another article I wrote here.

Liquorice ???

In 2005, a vet in Touranga, New Zealand wrote a note published in a journal there. It regarded the possible beneficial effects of licorice in pets that suffer from Addison's disease. I know nothing of its use or effect for that purpose. Be cautious about giving anything to your pet in excessive amounts - particularly based on a single article. You can read Dr. J's letter here.

What
Medications Will My Pet Be Needing ?

Most
dogs with Addison’s disease will need to be medicated for
the rest of their life. Most will require two forms of medication, one
to keep their blood potassium and sodium levels (blood
electrolytes) optimal and another to replace the cortisol
that they can no longer produce. The body’s cortisol needs
change, depending on stress, exertion, exercise and the pets changing
environment. So one dose will not fit all situations your pet will
encounter over the years it lives with Addison’s disease.

If
your dog has typical Addison’s disease, where both aldosterone
and cortisol are deficient, most veterinarians will stabilize your
pet with monthly injections of desoxycorticosterone pivalate (DOCP).
It is sold under the trade name, Percorten-V.
Percorten replaces the mineralcorticoid, aldosterone, that dogs
with typical Addison’s disease no longer produce in sufficient
quantities.

Dogs
with typical Addison’s disease also need as synthetic corticosteroid
to replace the cortisol they no longer produce in sufficient quantities.
Oral prednisone or prednisolone is the most common cortisol-substitute
that veterinarians give for that.There
is a human oral medication, fludrocortisone acetate (Florinef),
that replaces both the aldosterone and the cortisol with a single
drug. However, it has been quite expensive. So it has not been as widely
used as the Percorten/prednisolone combination therapy. Fludrocortisone
has now gone off-patent and is available in less expensive, generic
form. So perhaps it will become the treatment of choice.

Dogs
with secondary or atypical Addison’s disease still produce
sufficient aldosterone. So they only need a cortisol-substitute, like prednisolone, to maintain their health. Cortisol
is a compound that the pet’s adrenal glands meter into its
bloodstream in ever-changing amounts designed to meet its current
metabolic needs. So the dose of corticosteroid replacement you give
your pet needs to also vary according to the dog’s anticipated
metabolic needs. It will need more when you anticipate strenuous
exercise, boarding, grooming, or any situation that puts excess
demands on its body. It will need less when its body is unstressed
and at rest.

All
pets with Addison’s disease need periodic monitoring of their
blood potassium and sodium levels. Once you know how your pet is
reacting to its medications, those tests can be done less frequently.
Over time, expect the required dose of each medication to change. Many
pet owners have heard that corticosteroid medications, like prednisolone,
should not be given every day because they cause adrenal gland suppression
(cause the adrenal glands to “get lazy”).
That is true in dogs with healthy adrenal glands. But dogs that
cannot make sufficient natural cortisol need their replacement medication
every day. Don’t stop just because your dog appears happy
for a few days without it. If
your pet begins to drink and urinate excessively (in
the absence of kidney disease or diuretic medications); if it gains considerable weight; if it is subject to repeat infections; or if its blood sugar, liver function or kidney function tests (BUN, creatinine) results increase, its
cortisol replacement dose might need to be lowered.

How
Long Can My Dog Live With Addison’s Disease ?

The
problems that Addison’s disease causes in sodium and potassium
levels and a lack of cortisol are straightforward and quite correctable
with medications. So your pet has the potential to live a very long
life. How long a life depends entirely on how well Addison’s
disease is managed. Your dog will depend on you to protect it from
stress and to tailor its medication dose and frequency to its daily
needs. That is not something your veterinarian can do for you on a day-to-day basis. Every
dog will be different. But after a period of time on its medications,
and after enough blood tests have been run to see how these medications
are affecting it, you will be able to make the fine adjustments your pet will need to return to its favorite activities and enjoyments. Concentrate
on providing your pet with as low stress a lifestyle as possible,
plenty of love, good nutrition, adequate exercise, weight control, and attention
to the other health issues that life invariably brings our way. You can read the advice human physicians give to their Addison's patients here. They apply to your pet as well.